A putative cAMP-binding protein in Trypanosoma brucei cooperates with FLAM3 to promote flagellar connection and cell morphogenesis.

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  • Author(s): Zhou Q;Zhou Q; Nguyen PV; Nguyen PV; Li Z; Li Z
  • Source:
    The Journal of biological chemistry [J Biol Chem] 2024 Nov; Vol. 300 (11), pp. 107856. Date of Electronic Publication: 2024 Oct 05.
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
      Trypanosoma brucei brucei*/metabolism ; Flagella*/metabolism ; Protozoan Proteins*/metabolism ; Protozoan Proteins*/genetics; Morphogenesis ; Cyclic AMP/metabolism
    • Abstract:
      Trypanosoma brucei is a flagellated parasitic protozoan, and within the insect vector the parasite transitions from the trypomastigote form to the epimastigote form by repositioning its mitochondrial genome and relocating the flagellum. The mechanisms underlying such morphology changes are still poorly understood, but several flagellum-localized proteins are involved in this process by modulating the flagellum attachment zone (FAZ) that adheres the flagellum to the cell membrane. We report here a putative cAMP-binding protein named cAMP-BP1, which promotes flagellar connection and morphology transition. cAMP-BP1 contains two cyclic nucleotide-binding domains and five calcium-binding C2 domains and localizes to the flagella connector and the new FAZ tip. Depletion of cAMP-BP1 in the trypomastigote form of T. brucei causes major morphology changes, generating epimastigote-like cells with repositioned kinetoplast and relocated flagellum. At the flagella connector and the new FAZ tip, cAMP-BP1 associates with FLAM3, a regulator of morphology transition, depends on the latter for localization, and is required for FLAM3 localization to the flagella connector. Knockdown of cAMP-BP1 inhibits FAZ elongation and disrupts flagellar connection by impairing flagella connector structural integrity. These results identify a flagella connector- and new FAZ tip-localized protein as a regulator of morphology transition and flagellar connection in trypanosomes and uncover its functional interplay with FLAM3 to promote FAZ elongation for maintaining trypomastigote morphology.
      Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
      (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
    • Grant Information:
      R01 AI101437 United States AI NIAID NIH HHS; R01 AI118736 United States AI NIAID NIH HHS
    • Contributed Indexing:
      Keywords: Trypanosoma brucei; cAMP-binding protein; epimastigote; flagellum; flagellum attachment zone; trypomastigote
    • Accession Number:
      0 (Protozoan Proteins)
      E0399OZS9N (Cyclic AMP)
    • Publication Date:
      Date Created: 20241006 Date Completed: 20241203 Latest Revision: 20241203
    • Publication Date:
      20250114
    • Accession Number:
      PMC11555346
    • Accession Number:
      10.1016/j.jbc.2024.107856
    • Accession Number:
      39369991